The function of bone is to support body against gravity and to conduct movement. As the largest reservoir of calcium in the body, the bone also maintains the balance of calcium in the body. Because of having movement function and maintaining the balance of calcium in the body, the renewal and resorption of bone and the bone will be made repeatedly. During childhood and the adolescent, bone formation is more important than bone resorption, thus bone grows larger, heavier and denser.
The following briefly states how the bone goes through its life cycle through different stages in bone remodeling.
The bone remodeling is mainly regulated by chondrocyte, osteoblast and osteoclast. The bone remodeling can be divided into three stages. That is, (1) bone renewal and growth due to intrachondral bone formation, (2) the cycle of remodeling bone formation and bone resorption to maintain quality and quantity; and (3) re-growth during bone injury such as fracture.
Each stages described above is regulated by various Ca2+-dependent enzymes, cytokines, gene transcription and other cellular regulation mechanisms to regulate activities the differentiation of the bone.
For example, the remodeling cycle involves bone resorption performed by osteoclasts. Osteoclasts remove the old or worn-out mineralized bone. Bone resorption is initiated when osteoclasts receive signals from the surface of bone that are stimulated by enzymes or cytokines. On the other hand, osteoblasts rebuild new bone tissue by laying down an unmineralized matrix, called osteoid, which will eventually form new mineralized bone.
When this rebuilding is complete, the area of bone remodeling rests until the next remodeling cycle begins. Under normal condition, bone resorption and formation are performed at the same time, thus the bone can renew without affecting bone's function.
As we march into the elder-populated society, osteoporosis that happens at youth is drawing more and more attention. Osteoporosis is not a disease of change in the bone component, but a decrease of bone mass. The decrease of bone density and bone strength make one more susceptible to accident and the resulting fracture or bone damages. The primary cause of osteoporosis is the imbalance of bone remodeling, the overly increase of osteoclasts and bone resorption. In addition, many female patients at menopause suffered from osteoporosis, suggesting that the lower of sex hormone (i.e. estrogen) is one of the causes of osteoporosis.
There are currently many agents available for osteoporosis on the market. For example, estrogen can treat osteoporosis. Therefore, steroid enzymes and derivatives similar to chemical structure of estrogen are regarded as potential agents for treating osteoporosis. In theory, the enzymes are not only applied to treat osteoporosis, but decrease the side effects caused by estrogen. However, the substantive examination has not studied yet.
In addition, JP H04-352795 disclosed agents that are hydroxyl containing steroidal hormones, having bone resorption antagonist or bone formation stimulatory activity. The agent acts as bone resorption antagonist. However, the actual experimental data have not been disclosed. JP H07-215878 disclosed an agent containing mepitiostane and epitiostanol as active ingredients for treating osteoporosis.
JP H08-12580 is related to a synostosis promotor containing a specific active vitamin D and its derivative as active ingredients, promoting bone-repairing step after extension of bone, cut of bone, fracture, etc., and useful for shortage of treating period and prevention and treatment for re-fracture.
JP H11-60489 disclosed a medicine for preventing/treating osteoporosis which enhances density and strength of bone without elevating the concentration of calcium in blood, by including an active type vitamin D and bisphosphonic acid as active ingredients.
However, the prior art above provides chemical compounds only, therefore cannot sufficiently treat osteoporosis.